INTRODUCTION:

Based on solubility and permeability, the Biopharmaceutical Classification System (BCS) was created. Solubility, permeability, and dissolution are three important factors that influence medication bioavailability.

The pace and extent to which a medicine is present in systemic circulation at any one time is referred to as bioavailability. The majority of medication belong to these class of pharmaceuticals, which are those that are weakly soluble.

High solubility and high permeability, low solubility and high permeability, high solubilityand low permeability, low solubility and low permeability are the four kinds of BCS drugs. The dissolving rate can be increased to increase the drug's solubility.Improved dissolving rate of poorly soluble medicines by increasing surface area through particle size reduction leads in low bioavailability. The solid dispersion approach is extensively employed in this scenario. The solid dispersion method is defined as the fusing, solvent, or melting of one or more solid particles in an inert matrix.In pharmacological dosage forms, solubility plays an important role. Solubility is defined as the ability of a substance to dissolve in a specific solvent at a specific temperature. More than 90% of drugs delivered orally rely on the solubility characteristic for absorption, bioavailability, and pharmacokinetic profile. Good solubility indicates that the substance is easily dissolved and absorbed. The pharmaceutical business faces a dilemma when it comes to developing dosage forms since they are poorly soluble and have a poor dissolution profile. Micronization, coacervation, complexation solid dispersion, and co-solvent are some of the solubilization strategies available for enhancing solubility and permeability. Solubility can also be increased by altering the physical structure of the medicine at the molecular level.Solid dispersions are the most appealing option for increasing bioavailability of medicines that are poorly water soluble. Solid dispersions are defined as the solid dispersion of one or more active substances in a matrix by various methods such as fusing or melting solvent technique. Solid dispersions are divided into six groups: solid solutions, eutectic mixtures, glass suspensions, precipitations, complexes, and combinations of the first five.Solid dispersions boost the wettability and porosity of pharmaceuticals by reducing particle size. Solubility and dissolving rate are improved by porosity and wettability. There are numerous manufacturing processes described in the literature, including fusion, solvent evaporation, hot melting extrusion, co-grinding, and supercritical procedures. Aqueous solubility is a major stumbling block to excellent bioavailability. Many supercritical procedures. Aqueous solubility is a major stumbling block to excellent bioavailability. Manytechniques have been investigated in drug development research to tackle this difficulty.¹

What Is Solubility..?

Quantitatively it is termed as concentration of solute in concentrated solution at a certain temperature.

In Qualitative way Solubility is a spontaneous interaction of two or more substances to form a homogenous molecular dispersion.²

Importance of Solubility:

The therapeutic effectiveness of a medicine is determined by its bioavailability and, eventually, its solubility. Solubility is a crucial characteristic for achieving the appropriate drug concentration in the systemic circulation and demonstrating pharmacological response. Only 8% of novel drug ideas have both good solubility and permeability at the moment. Nearly 40% of newly identified chemical entities are insoluble in water. More than a third of the medications listed in the United States Pharmacopoeia are water-insoluble or poorly water-soluble. Low aqueous solubility is a major issue in the development of novel chemical entities' formulations. Any medicine that needs to be absorbed must be in the form of an aqueous solution at the absorption site. Improving drug solubility and hence oral bioavailability is one of the most difficult aspects of the drug development process, especially for oral drug delivery systems. In the literature, several approaches for enhancing the solubility of weakly water soluble medicines have been identified. The techniques are determined by criteria such as the properties of the drug in issue, the type of the excipients to be employed, and the nature of the intended dosage form.³

Process of solubilization:

· The holesgets open in the solvent.

· The molecules of the solid starts to break down away from the bulk.

· The freed solid molecule in the solvent gets integrated into the hole.⁴

Factors Affecting Solubility of Solute in Liquids:

1. Temperature:

The temperature affects the solubility of solids in liquids. If heat is absorbed during the solution process, the solute's solubility increases as the temperature rises. This is true for the majority of the salts. If a solute emits heat throughout the solution process, the solute's solubility will decrease as the temperature rises.

2. Molecular structure of solute:

A little alteration in a compound's molecular structure can have a significant impact on its solubility in a given liquid.Introducing a hydrophilic hydroxyl group, for example, can result in a significant increase in water solubility; moreover, converting a weak acid to its sodium salt results in a significantly higher degree of ionic dissociation of the compound when it dissolves in water. The overall interaction between the solute and the solvent is significantly increased, resulting in an increase in solubility. Furthermore, the esterification of a medication reduces its solubility.

3. Nature of solvent:

The importance of the statement 'like dissolves like', and in relation to solubility parameters tells the nature of the solvent.In addition, these mixtures are often used in pharmaceutical practice to obtain aqueous-based systems which contain solutes in maximum quantity /in excess amount of their solubility in pure water. By using these examples of cosolvents like ethanol or propylene glycol, that can be miscible with water and which becomes a better solvents for the solute.

4. Crystal characteristics:

Different crystalline forms of the same substance, which are known as polymorphs, consequently possess different lattice energies, and these variations are reflected by changes in other properties.The effect of polymorphism on solubility is specifically important from a pharmaceutical point of view, by using a metastable polymorph because it provides a means of increasing the solubility of a crystalline material along with its rate of dissolution. The absence of crystalline structure that is mostly associated with a so-called amorphous powder may also lead to an increase in the solubility of a drug compared to that of its crystalline form.

5. Particle size of the solid:

Because of the variations in interfacial free energy that accompany the dissolution of particles of various sizes, a substance's solubility increases as particle size decreases. The increase in solubility with decrease in particle size stops when the particles have a very small radius than required, and any further decrease in size leads to decrease in solubility.

6. pH:

The proportion of unionised acid molecules in a solution of a weakly acidic medicine or a salt of such a drug increases when the pH of the solution is dropped. Precipitation may occur as the solubility of the unionized species becomes lower than that of the ionized form. In the case of solutions containing weakly basic medicines or their salts, however, an increase in pH promotes precipitation.

7. Complex formation:

The addition of a third material, which forms an intermolecular complex with the solute, can enhance or reduce the apparent solubility of a solute in a given liquid. The apparent change in the solubility of the original solute is determined by the solubility of the complex.

8. Solubilizing agent:

When the concentrations of these agents approach certain thresholds, they can form huge aggregates or micelles in solution.The centre of these aggregates mimics a separate organic phase in aqueous solution, and organic solutes can be taken up by the aggregates, resulting in an apparent increase in their water solubility. This phenomenon is known as solubilization. Because the core of the aggregates in these systems is more polar than the majority of the organic solvent, a similar phenomena occurs in organic solvents containing dissolved solubilizing agents.The apparent solubility of polar solutes in organic solvents is increased when they are taken up into these areas.

9. Polarity:

The solubility is affected by the polarity of the solute and solvent molecules.Non-polar solute molecules dissolve in non-polar solvents, while polar solute molecules dissolve in polar solvents. The polar solute molecules have two ends: a positive and a negative end. Positive ends of solvent molecules will attract negative ends of solute molecules if the solvent molecule is similarly polar.The dipole dipole interaction is one type of intermolecular force. The other forces are known as London dispersion forces, in which the positive nuclei of the solute molecule's atoms attract the negative electrons of the solvent molecule's atoms. This allows the nonpolar solvent to interact with the solute molecules and solvate them.⁵

Techniques To Enhance Solubility:

1) Particle Size Reduction:

The bioavailability of a medicine is inextricably linked to its particle size. Increased solid surface area increases dissolving characteristics by lowering particle size. Milling techniques such as jet mills, rotor stator colloid mills, and others are used to reduce particle size. Because it does not modify the drug's saturation solubility, it is not suited for medications with a highdosage number. Micronization and nanosuspension are now used to reduce particle size. For particle size reduction, each process uses distinct equipment. In micronization, drug solubility is frequently inversely proportional to drug particle size. The increased surface area of the medication improves its dissolving characteristics by lowering particle size.^6,7

Advantages:

1. Liquid forms can be generated quickly for early stage testing (preclinical) and then converted to solids for later clinical development.

2. Low excipient-to-drug ratios are usually necessary.

3. If no strong surfactants are necessary for stabilisation, formulations are generally well tolerated.

4. Crystal structures are generally more chemically and physically stable than amorphous particles.

5. A way to consider in the case of refractory substances that have resisted earlier attempts to enhance their concentration.

Disadvantages:

1. There is a considerable tendency for particle agglomeration due to the high surface charge on discrete tiny particles.

2. It can be difficult to create a solid dosage form with a large payload without encouraging agglomeration.

3. Developing sterile intravenous formulations is significantly more difficult from a technical standpoint.

2) CO-SOLVENCY:

In order to increase the solubility of weakly soluble medications in water, they must be mixed with a water miscible solvent in which the drug is readily soluble. This is referred to as cosolvency, and the solvent employed in the process is referred to as cosolvent. The interfacial tension between the aqueous solution and the hydrophobic solute is reduced by the cosolvent system. Solvent mixing is another name for it. The addition of an organic co-solvent to water changes the solubility of medications dramatically. Cosolvents with a minor hydrocarbon region have hydrogen acceptor or donor groups. The hydrophobic hydrocarbon region frequently interferes with water's hydrogen bonding network, reducing intermolecular attraction and ensuring water solubility, whereas the hydrophilic hydrogen bonds ensure water solubility.

Solubilization by Co-solvents:

· Aqueous solubility is poor for weak electrolytes and non-polar compounds. The addition of water miscible solvents in which the medicine has strong solubility increases their solubility in water.

· Propylene glycol, polyethylene glycol, ethanol, and glycerin are examples of cosolvents that help to solubilize the medication in an aqueous medium.

· The polarity of the medication in relation to the solvent and cosolvent determines the solubilizing impact of cosolvency.^6,8

Advantages:

Simple and rapid to formulate and produce.

Disadvantages:

· The toxicity and tolerability of the solvent level administered, as with other excipients, must be considered.

· Dilution with aqueous media causes uncontrolled precipitation. Precipitates can be amorphous or crystalline, and their size varies. Many of the insoluble chemicals that he works with are unsuitable for intravenous delivery without the use of co-solvents. This is due to the medicines' severe insolubility in water and their inability to re-dispose following precipitation from the co-solvent mixture. There is a danger of embolism and local adverse effects at the injection site in certain cases.

· The chemical stability of the insoluble substance is worse than in a crystalline state, as it is with all solubilized forms.

3.) pH Ajustment:

Using a pH change, poorly water soluble pharmaceuticals containing portions of the molecule that can be protonated (base) or deprotonated (acid) may be dissolved in water. In theory, pH adjustments can be employed for both oral and parenteral administration.Because blood is a powerful buffer with a pH between 7.2 and 7.4, the poorly soluble medication may precipitate after intravenous injection.The buffer capacity and tolerability of the chosen pH are crucial factors to consider when evaluating the approach's suitability.Because the pH in the stomach is around 1 to 2, and the pH in the duodenum is between 5-7.5, the degree of solubility is likely to be changed as the drug moves through the intestines after oral delivery.The best candidates are ionizable chemicals that are stable and soluble following pH adjustment. Acids, bases, and zwitterionic compounds are all possible.It can be used on crystalline and lipophilic poorly soluble substances alike.Solubilized excipients that raise the pH of the environment within a dosage form, such as a tablet or capsule, to a level higher than the pKa of weakly acidic pharmaceuticals increase the drug's solubility; similarly, excipients that function as alkalizing agents may increase the solubility of weakly basic drugs.Because the solubility of the poorly soluble medicine is improved as compared to water alone, the proportion of orally absorbed drug may be raised if compounds can permeate through the epithelium orally.To boost the solubility of a poorly soluble medication, pH modification is commonly combined with co-solvents. Because of the higher concentration gradient and increased surface area for dissolution, bioavailability can be increased when the precipitate is fine or amorphous after dilution.Bioavailability may not be significantly boosted when the medication precipitates into poorly soluble particles that require dissolving and do not rapidly redissolve.Because of its universality and relative simplicity, pre-clinical pH adjustment is a suitable tool for assessing the efficacy of poorly soluble medications and is used extensively in Survey.The interpretation of the data may be misleading if the poorly soluble drug precipitates uncontrollably after contact with a pH at which the drug is substantially less soluble (oral and parenteral).^6,11-13

Advantages:

1. Simple to formulate and analyse.

2. Simple to produce and fast track.

3. Uses small quantities of compound, amenable to high throughout evaluations.

Disadvantages:

1. Precipitation risk when diluted in aqueous media with a lower pH than the compound's solubility. This may produce emboli intravenously, and it may cause variability orally.

2. Tolerance and toxicity (local and systemic) associated with non-physiological pH and extreme pHs

3. A dissolved medication in an aqueous environment, like all solubilized and dissolved systems, is usually less chemically stable than crystalline solid formulations. The chosen pH could hasten hydrolysis or stimulate other degradation processes.

4.) SOLID DISPERSION³⁴

Solid dispersions are an effective way to improve medication solubility, absorption, and therapeutic efficacy in dosage forms in the pharmaceutical industry. Solid dispersion is a phrase used to describe a collection of solid goods made up of at least two separate components, usually a hydrophilic matrix and a hydrophobic medication. Polyvinylpyrrolidone, polyethylene glycols, and PlasdoneS630 are the most often utilised hydrophilic carriers for solid dispersions.Surfactants are frequently utilised in the creation of solid dispersion. Tween-80, Docusate sodium, Myrj-52, Pluronic-F68, and Sodium Lauryl Sulphate were utilised as surfactants. Solid dispersion utilising suitable hydrophilic carriers can enhance the solubility of celecoxib, halofantrine, and ritonavir. To improve their aqueous solubility, hydrophobic medicines can be solid dispersed using a variety of ways.

Hot melt method (fusion method):

The simplicity and cost-effectiveness of this direct melting technology are its key advantages. Sekiguchi and Obi were the first to suggest the melting or fusing procedure for generating fast-release solid dispersion dosage forms. The physical mixture of a medication and a water-soluble carrier was heated until it melted in this procedure. The melting fluid was then swiftly cooled and hardened in an ice bath while being vigorously stirred. The resultant solid mass was crushed, pulverised, and sieved, and tabletting agents were used to compress it into tablets. The melting point of a binary system is determined by its composition, which includes the carrier chosen and the drug's weight fraction in the system. The miscibility of the drug and the carrier in molten form is a key requirement for the creation of solid dispersion using the hot melt method. Also another important requisite is the thermostability of the drug and carrier.

Solvent Evaporation Method:

Tachibana and Nakumara were the first to combine the medication and the carrier in a single solvent, then evaporate the solvent under vacuum to obtain a solid solution. As a result of this, they were able to generate a solid solution of the highly lipophilic -carotene in the very water soluble carrier polyvinylpyrrolidone. Using the solvent evaporation technique, many researchers investigated the solid dispersion of meloxicam, naproxen, and nimesulide. These findings show that the above-mentioned approach can be used to enhance and stabilise solid dispersions of pharmaceuticals that are weakly water soluble. The fundamental advantage of the solvent approach is that due to the low temperature required for the evaporation of organic solvents, thermal degradation of medications or carriers can be avoided. The higher cost of preparation, the difficulty in completely removing liquid solvent, the possibility that the supposedly negligible amount of solvent has an adverse effect on the chemical stability of the drug, the use of a common volatile solvent, and the difficulty in reproducing crystal forms are all disadvantages of this method.

Hot melt extrusion:

Hot melt extrusion is similar to fusion with the exception that the extruder causes significant mixing of the components. Miscibility of medication and matrix, just like in the traditional fusion method, can be a concern. For heat-sensitive materials, large shear forces resulting in a high local temperature in the extruder are an issue. In comparison to the classic fusion approach, however, this technology allows for continuous production, making it appropriate for large-scale production. Hence the product becomes easier to handle as the shape can be modified to the next processing stage without grinding at the extruder's outlet.^14-20

5) Inclusion Complex Formation Based Techniques:

The inclusion complex creation technique has been used more accurately among all the solubility enhancement strategies to improve the aqueous solubility, dissolving rate, and bioavailability of weakly water soluble medicines. Inclusion complexes are produced when a nonpolar molecule or a nonpolar section of a molecule (referred to as a guest) is inserted into the cavity of another molecule or group of molecules (known as host). Cyclodextrins are the most prevalent host molecules. Cyclodextrins are cyclic oligomers formed by the enzymatic breakdown of starch by cyclodextrin-glycosyltransferase (CGT). Cyclodextrins are cyclic oligosaccharides that are non-reducing, crystalline, and water soluble. Cyclodextrins are made up of glucose monomers stacked in a ring in the shape of a donut.-Cyclodextrin, -Cyclodextrin, and -Cyclodextrin are three naturally occurring CDs. The inclusion complex of cyclodextrins can increase the solubility and oral bioavailability of Glipizide, Rofecoxib, Piroxicam, and Carvedilol. Inclusion complexes of weakly water soluble medicines with cyclodextrins can be prepared using a variety of approaches.

Dendrimers have the ability to improve the solubility of drugs that are poorly water soluble. The interactions between the surface amine groups of the dendrimer molecule and the carboxyl group of any medicine could be to blame. The drug solubility is inversely related to the temperature and directly proportional to the dendrimer concentration, which is most likely owing to an increase in the amount of surface amines accessible to interact electrostatically with drug molecules.²⁵

Kneading method:

The CDs are impregnated with a small amount of water or hydroalcoholic solutions and then transformed into a paste using this procedure. The medicine is then mixed into the paste and kneaded for a set amount of time. After that, the kneaded mixture is dried and, if necessary, sieved. The use of the complexation approach to improve the solubility. Kneading on a laboratory scale can be accomplished with a mortar and pestle. Kneading can be done on a huge scale with the help of extruders and other devices. This is the most frequent and straightforward approach for creating inclusion complexes, and it has a very cheap manufacturing cost.

Lyophilization/ Freeze drying technique:

The lyophilization/freeze drying approach is recommended for producing a porous, amorphous powder with a high degree of drug-CD interaction. Through a first freezing and subsequent drying of the solution comprising both medication and CD at low pressure, the solvent system from the solution is removed. This approach can successfully convert thermolabile compounds into complex forms. This technique's drawbacks include a lengthy processing time and a powdered result that flows poorly. Lyophilization/freeze drying is a process that involves molecular mixing of medication and carrier in a shared solvent as an alternative to solvent evaporation.

Microwave irradiation method:

Using a microwave oven, this process involves a microwave irradiation reaction between the medication and the complexing agent. In a round bottom flask, the medication and CD are dissolved in a certain molar ratio in a mixture of water and organic solvent in a specified proportion. In a microwave oven, the mixture is reacted for one to two minutes at 60°C. Following the completion of the reaction, a sufficient amount of solvent mixture is added to thereaction mixture to eliminate any remaining uncomplexed free drug and CD. The precipitate is then separated using Whatman filter paper and dried for 48 hours in a vacuum oven at 40°C, designed a quick dissolving formulation using several superdisintegrants by combining ziprasidone hydrochloride with beta-cyclodextrin and hydroxypropyl beta-cyclodextrin. Microwave irradiation is a unique technology for industrial scale preparation since it has the advantages of a faster reaction time and a higher product yield.^14,21-24

6.) SALT FORMATION:³²

· The most common and successful approach of improving the solubility and dissolution rates of acidic and basic medicines is salt production.

· Salts of acidic and basic medicines have higher solubilities than their acid or base counterparts in general.

· Under gastrointestinal (GI) pH circumstances, dissolving rates of salt forms of various weakly acidic substances were substantially higher than those of their respective free acid forms for solid dose forms.

· Strong acid salts of basic medications like atropine and alkali metal salts of acidic drugs like penicillins are more water soluble than the parent drug.^5,6

7) Micellar Solubilization:

· Surfactants have also been used successfully to increase the dissolving performance of poorly soluble medicinal formulations.

· Surfactants can help lipophilic medications dissolve better in aqueous media by lowering surface tension.

· They can also help to keep drug suspensions stable.

· Micelle formation happens when the concentration of surfactants surpasses their critical micelle concentration (CMC), which is typically in the range of 0.05% to 0.10% for most surfactants. Micellisation is a procedure that improves the solubility of medications that aren't easily soluble.

· Polysorbates, polyoxyethylated castor oil, polyoxyethylated glycerides, lauroylmacroglycerides, and mono- and di-fatty acid esters of low molecular weight polyethylene glycols are all examples of non-ionic surfactants.

· Surfactants are frequently employed to stabilise microemulsions and suspensions that contain medicines.

· Micellar solubilization is a popular method for dissolving medications that are difficult to dissolve.¹⁴

8) Sono-Crystallization:

Melt sonocrystallization is a relatively recent method of particle engineering. The crystallisation process is done in this method by using ultrasonic energy in the range of 20 to 100 kHz. Ultrasound energy was previously used in the pharmaceutical business to boost the solubility of sparingly soluble drugs. The first nucleation stage of crystallisation is influenced by an ultrasound system. Ultrasonication induces particle disaggretion or deagglomeration. Cavitation is an important ultrasonic phenomena. The energy of ultrasound causes repeated compression and expansion in sonocrysatllization. The bubble forms, swells, and then crashes after numerous cycles. The energy is produced as a result of bubble collapses. The breaking of particles is caused by this energy. This results in crystallisation that is highly repeatable and predictable.

Applying ultrasound to crystallization results in:

· Nucleation happens when crystallisation overcomes the compound's inclination to re-dissolve in the solution at the lowest degree of super saturation.

· Narrowing of the metastable zone width.

· Narrow particle size distribution.

· The amount of cooling required to accomplish crystallisation is reduced.

· Highly repeatable and predictable crystallization.

· Polymorph control

9) HYDROTROPHY³³

Hydrotrophy is a solubilization method in which a significant amount of a second solute is added, resulting in an increase in the first solute's water solubility. Alkali metal salts of various organic acids make up the solute. Ionic organic salts are hydrotropic agents. Salts that improve the solubility of a solute in a particular solvent are called to "salt in," while salts that decrease solubility are said to "salt out." The "salting in" of non-electrolytes dubbed "hydrotropic salts" is caused by many salts with large anions or cations that are themselves extremely soluble in water, a process known as "hydrotropism." Hydrotropic solutions are non-colloid and have a weak contact between the hydrotropic agent and the solute. The term "hydrotrophy" refers to the rise in water solubility that occurs when a large number of compounds are present. Complexation, which involves a mild interaction between hydrotrophic compounds such sodium benzoate, sodium acetate, sodium alginate, and urea and poorly soluble drugs, is more closely linked to improving solubility.⁶

Advantages of Hydrotropic Solubilization Technique:

1. Because the solvent property is independent of pH, has excellent selectivity, and does not require emulsification, hydrotropy is seen to be preferable to alternative solubilization methods such as miscibility, micellar solubilization, cosolvency, and salting in.

2. It merely takes a few minutes to combine the medication and the hydrotrope in water.

3. It does not necessitate modifying hydrophobic medicines chemically, using organic solvents, or preparing an emulsion system.

4. In solution, the hydrotropes are known to self-assemble.

5. Because a wide variety of substances have been reported to display hydrotropic behaviour, classifying hydrotropes on the basis of molecular structure is problematic.

10) Nanosuspension:

The technology of nanosuspension has been developed as a possible contender for the efficient delivery of hydrophobic medicines. This method is used on pharmaceuticals that are poorly soluble in both water and oils. A pharmaceutical nanosuspension is a biphasic system made up of nano-sized drug particles stabilised by surfactants for use in the mouth, on the skin, or in the lungs. Solid particles in nanosuspensions typically have a particle size distribution of less than one micron, with an average particle size ranging between 200 and 600 nm. Some of the ways for preparing nanosuspension include media milling (Nanocrystals), high pressure homogenization in water (Dissocubes), high pressure homogenization in nonaqueous media (Nanopure), and a combination of precipitation and high pressure homogenization (Nanopure) (Nanoedege).

Precipitation Techniques:

The medicine is dissolved in a solvent, which is then added to a nonsolvent to precipitate the crystals in the precipitation procedure. The utilisation of simple and low-cost equipment is the primary benefit of the precipitation technique. The main difficulty with this method is that the growth of the drug crystals must be regulated throughout the precipitation process with the addition of a surfactant to avoid the development of microparticles. The medication must be soluble in at least one solvent, and this solvent must be miscible with nonsolvent in order for this precipitation process to work. Furthermore, the precipitation approach is ineffective for medicines that are poorly soluble in both aqueous and nonaqueous environments. To increase the dissolution rate and oral bioavailability, a nanosuspension generated by the precipitation process is utilised.

Media milling (Nanocrystals or Nanosystems):³¹

The nanosuspensions are manufactured using high-shear media mills, according to the method first described and reported. The milling chamber, which contains milling material, water, medication, and stabiliser, is rotated at a very high shear rate for several days at controlled temperatures (at least 2-7 days). Glass, zirconium oxide, or strongly cross-linked polystyrene resin make up the milling media. The impaction of the milling media with the drug produces high energy shear pressures, resulting in the breaking of microparticulate drug into nanosized particles. Poorly soluble medicines, such as Cilostazol, have a slow rate of dissolution and a low bioavailability.

High pressure homogenization:

Many poorly water soluble medicines have been nanosuspended using high pressure homogenization. In the high pressure homogenization procedure, a medicine and surfactant suspension is pressed under pressure through a nanosized aperture valve of a high pressure homogenizer. The principle of this approach is based on aqueous phase cavitation. The cavitation forces of the particles are sufficient to transform the drug microparticles into nanoparticles. The need for small sample particles before loading, as well as the fact that several cycles of homogenization are necessary, are also concerns with this procedure. R.H. Müller's DissoCubes technology, which uses a piston-gap-type high pressure homogenizer, is an example of this technique.

Combined precipitation and homogenization (Nanoedege): ³¹

The precipitated drug nanoparticles have a proclivity for continuing to develop into microcrystals. High-energy forces are required to process them (Homogenisation). They are entirely amorphous, slightly amorphous, or completely crystalline, all of which provide problems with long-term stability and bioavailability. As a result, the precipitated particle dispersion is homogenised, preserving the particle size achieved after the precipitation process.¹⁴

CONCLUSION:

For poorly soluble medicines, solubility is a critical factor in oral bioavailability.

Because drug dissolution is the rate-determining step for oral absorption of poorly water-soluble medicines, which can have an impact on in vivo absorption, solubility augmentation is required.

Various approaches, such as those outlined above, can now be used to improve the solubility of poorly soluble medicines.

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Received on 06.04.2022 Modified on 16.07.2022

Res. J. Pharma. Dosage Forms and Tech.2022; 14(4):315-323.

DOI: 10.52711/0975-4377.2022.00052